Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells

Creative Commons License

Cai B., Kim D., Akhand S., Sun Y., Cassell R. J., ALPSOY A., ...More

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol.141, no.43, pp.17057-17061, 2019 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 141 Issue: 43
  • Publication Date: 2019
  • Doi Number: 10.1021/jacs.9b08085
  • Journal Name: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.17057-17061
  • Middle East Technical University Affiliated: No

Abstract

We report the selection of DNA-encoded small molecule libraries against protein targets within the cytosol and on the surface of live cells. The approach relies on generation of a covalent linkage of the DNA to protein targets by affinity labeling. This cross-linking event enables subsequent copurification by a tag on the recombinant protein. To access targets within cells, a cyclic cell-penetrating peptide is appended to DNA-encoded libraries for delivery across the cell membrane. As this approach assesses binding of DELs to targets in live cells, it provides a strategy for selection of DELs against challenging targets that cannot be expressed and purified as active.